Table 3. Summary of Candidate Glutamatergic Neurotransmission Modulating Agents for the Treatment of OCD.

Drug Name	FDA Approval	Mechanism(s) of Action	OCD Studies	Effectiveness
riluzole	ALS	reduction of synaptic glutamate release via multiple presynaptic mechanisms; stimulation of glutamate uptake by astocytes	Pittenger et al. 2008 [135] Coric et al. 2005 [130] Grant et al. 2007 [132] Coric et al. 2003 [129] Coric et al. 2007 [134]	slightly more than half of the 32 total OCD patients treated open-label with riluzole have shown significant improvements
topiramate	epilepsy	block of voltage-dependent Na+ and K+ channels; reduction of AMPA/kainate receptor channel conductance; positive modulatory actions on GABAA receptors	Van Ameringen et al. 2006 [137 ] Hollander & Dell'Osso, 2006 [138 ] * Ozkara et al. 2005 [140 ]	12/17 cases showed improvements; topiramate induced OCD symptoms in one isolated case report
lamotrigine	epilepsy, bipolar disorder	inhibition of voltage-dependent Na+ channels to reduce synaptic glutamate release from neurons	Kumar & Khanna, 2000 [139 ] * Alkin et al. 2007 [141 ] * Kuloglu et al. 2008 [142 ] * Kemp et al. 2007 [143 ]	1/8 OCD patients showed benefit; lamotrigine induced OCD symptoms in 7 cases from 3 other studies
N-acetylcysteine	acetaminophen toxicity	stimulation of the glial cystine/glutamate exchanger resulting in activation of mGluR2 receptors which dampens presynaptic glutamate release from neurons during bouts of excessive neuronal activity	Lafleur et al. 2006 [146 ]	a single case report indicates potential benefit as augmenting agent
LY354740	N/A	agonist of type II metabotropic glutamate receptors; dampens presynaptic glutamate release from neurons during bouts of excessive neuronal activity	No studies in OCD patients	N/A
memantine	Alzheimer's disease	NMDA-type glutamate receptor open-channel blocker (moderate antagonist relative to dizocilpine)	Pasquini & Biondi, 2006 [150 ] Poyurovsky et al. 2005 [151 ]	2/3 OCD patients treated with memantine showed improvements
amantadine	influenza A virus infection, Parkinson's disease	NMDA-type glutamate receptor open-channel blocker (moderate antagonist relative to dizocilpine)	No studies in OCD patients	N/A
dizocilpine (MK-801)	N/A	NMDA-type glutamate receptor open-channel blocker (high-affinity antagonist relative to memantine/amantadine)	No studies in OCD patients	exacerbates OCD symptoms in the D1CT mouse model [154 ]
D-cycloserine (DCS)	antibiotic treatment for tuberculosis	partial agonist of NMDA-type glutamate receptors	Wilhelm et al. 2008 [160 ] Kushner et al. 2007 [161 ] ˆ Storch et al. 2007 [162 ]	optimal DCS administration may improve treatment response when combined with behavioral therapy

^*OCD symptoms induced by drug treatments in patients that were not previously diagnosed with OCD, therefore these are not technically OCD studies per se.

^ˆThis study found no evidence of improvements with DCS treatment, however it was suggested that these findings were due to sub-optimal timing of DCS administration.

N/A, not applicable.